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Pure Appl. Chem., 2013, Vol. 85, No. 7, pp. 1499-1513

Published online 2013-05-23

Photo-click chemistry strategies for spatiotemporal control of metal-free ligation, labeling, and surface derivatization

Selvanathan Arumugam1, Sara V. Orski1,2, Ngalle Eric Mbua3, Christopher McNitt1, Geert-Jan Boons3, Jason Locklin1,2 and Vladimir V. Popik1*

1 Department of Chemistry, University of Georgia, Athens, GA 30602, USA
2 Faculty of Engineering and the Center for Nanoscale Science and Engineering, University of Georgia, Athens, GA 30602, USA
3 Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA

Abstract: Three photo-click ligation strategies described in this account provide scientists with efficient and selective tools for derivatization of various molecules, polymers, and surfaces. Fast photochemical reactions that are utilized in these techniques permit spatiotemporal control of the process. The absence of activating reagents and catalysts, as well as compatibility with aqueous media, makes photo-click ligations suitable for biomedical applications. The first of these approaches relies on the photochemical decarbonylation of cyclopropenones to produce cyclooctynes. The latter undergo rapid catalyst-free strain-promoted azide–alkyne cycloaddition (SPAAC) to azide-tagged substrates. The second method is based on a very fast (>104 M–1 s–1) light-triggered hetero-Diels–Alder reaction and permits efficient derivatization of substrates bearing vinyl ether moiety. An even faster reaction between photochemically generated naphthoquinone methides (oNQMs) and thiols (~2 × 105 M–1 s–1) serves as a basis for a third method. This thiol photo-click chemistry allows for the selective derivatization of thiol-functionalized substrates or labeling of free cysteine residues in proteins. The thioether linkage produced by the reaction of oNQMs and a thiol is stable under ambient conditions, but can be cleaved by UV irradiation, regenerating free thiol. This feature permits the removal or replacement of immobilized compounds, as well as traceless substrate release.